This project will: determine the effects of chronic subcortical cerebrovascular disease on cortical integrity, quantify the effects of subcortical and cortical changes on cognition, and develop improved diagnostic markers which classify subcortical ischemic vascular dementia (SIVD) from Alzheimer's disease (AD). This project will use structural magnetic resonance imaging (MR/), arterial spin labeling perfusion MRI (pMRI), diffusion tensor imaging (DTI), and 1H magnetic resonance spectroscopic imaging (MRSI) on subjects with and without SIVD and AD, and follow them to autopsy. Our new finding is that SIVD subjects have reduced NAA in frontal cGM and higher NAA in hippocampus compared to AD. We will extend these results using new MRI techniques. The major hypotheses are: 1.) Both cross sectionally and longitudinally, frontal lobe cGM, volume, NAA, and perfusion will be decreased and ml increased, to a greater extent in SIVD compared with AD and will correlate with an increase of WML and subcortical lacunes, and a decrease of FA. In contrast, parietal and temporal cGM, NAA, and perfusion and hippocampal volume and NAA will be decreased, and mI increased, to a greater extent in AD compared with SIVD and will not be as closely correlated with WML, lacunes, and FA as are frontal lobe measures. 2.) Executive function will correlate with frontal lobe measures of gray matter integrity (cGM volume, NAA, mI and perfusion) and white matter integrity (WMLs, lacunes, and FA). Correlations in SIVD will be more significant than in AD. Frontal lobe measures of gray matter integrity and white matter integrity will predict, and correlate with, executive function decline in SIVD more than in AD. Memory function wfl| correlate with hippocampal measures (volume, NAA), language function will correlate with left parietal-temporal (cGM volume, NAA, perfusion, FA), visuospatial function will correlate with fight parietal-temproral (cGM volume, NAA, perfusion, FA). Measures of white matter integrity (WMLs, lacunes, FA) will correlate with memory, language function, and visuospatial function to a greater extent in SIVD than in AD. Measures ofhippocampal and temporo-parietaI cortical integrity will predict and correlate with memory, language, and visiospatiaI function to a greater extent in AD than in SIVD. 3.) Addition of NAA, mI, perfusion, and FA data will significant improve classification of AD from SIVD over structural MRI measures alone. Classifications will be performed using clinical diagnoses, and pathologically confirmed diagnoses from the Pathology Core.